Jet Lag: Timing is as important (or more so) than medications

Jet lag is a problem affecting the majority of people traveling rapidly or non-stop through multiple time zones. The more time zones traversed, the more likely one is to experience jet lag and the longer it takes to recover. East-West and West-East travel cause symptoms much more than North-South and South North travel because the problem is related to time zones more than distance flown. My experience is that the conventional “1 day of recovery per time zone traveled (over two time zones),” is pretty good. Unfortunately, many people have back-logged professional obligations and are missed by family who want and need attention. At this time of year, there are graduations and grandparents’ days at schools. Consequently, in addition to spouses and kids, there are important guests from out of town to host and entertain.

Jet lag can be minimized with some good planning, a little luck and, sometimes, with supplements such as melatonin, zolpidem (aka Ambien). Other medications such as modafinil (aka Provigil) are in the late stages of clinical trials and show promise for treating jet lag. Unlike melatonin and zolpidem, modafinil is used to aid in alertness rather than as an agent to improve the timing and quality of sleep. BTW--I have no financial interest or relationships with the manufacturers of these drugs!

There is no one recipe to combat jet-lag and people taking medications for conditions such as diabetes and hypertension. During air travel, a diabetic person should take his or her daily dose of insulin and eat according to local time (departure schedule). For a diabetic person traveling east-bound over multiple time zones, the day is effectively shortened. On arrival, the person should eat and administer insulin according to local time, but reduce the insulin dose by 1/3.  For travel west-bound, the day will lengthen and a second dose of insulin may administered with guidance from a glucose monitoring device.

Airlines such as Philippine Airlines (PAL) do a good job scheduling their flights from San Francisco to Manila and Manila to San Francisco. From Manila, flights generally leave at night and arrive at night, in San Francisco. My flight from Manila left at 10:30 PM and arrived in San Francisco at 10:30 PM.The evening meal was served almost immediately and I was able to sleep for virtually the entire first half of the flight.

Briefly, my strategy for combating jet lag on my return from the Philippines was a follows: 1. On the day of departure, I spent as much time outside as I could 2. I packed a meal so that I could eat as soon as I got on the plane and go straight to sleep. PAL uses the same strategy, so I had an entrée before my entrée. 3. I slept for six straight hours (thank you, zolpidem) on the plane and then stayed awake for the remaining flight time and until I got home (about 9 hours awake time). 4. Went to sleep as soon as I got home and woke up about 0630 and felt pretty darn good the next day—again, maximizing exposure to sunlight even coated with SPF 100+. 5. The main point is to try to get on the schedule of your destination as soon as possible. If it is not possible, then it is quite reasonable to consider pharmacological interventions. 6. Everyone is different.

Pharmacological Interventions

Melatonin:
Melatonin is a popular food supplement that is among the best studied interventions for circadian disturbances, including jet lag. It is not regulated the way most drugs are, since the FDA considers it to be a food supplement. Thus, formulations may vary in content, consistency, absorption and quality. I have to admit, I have not been a fan of melatonin, but need to reconsider my early prejudice now that more systematic and methodologically sound studies are being carried out. To date, the results of clinical trials are all over the place. In part, this is because flight attendants are often used as subjects and they have very complex, disordered sleep patterns. I do find it interesting that the doses used, typically 0.5mg to 5mg, result in serum concentrations orders of magnitude higher than those produced by anyone’s body.There are no data to suggest combining melatonin with prescribed medications such as zolpidem improves either one’s effects. Well described side-effects include hangovers or lethargy the next day, nightmares, confusion, headaches, but the percentages of people exhibiting these adverse reactions—while well-described-- is also not well quantified…People taking blood thinners such as warfarin and those with seizure disorders should be very cautious about using melatonin.

When I tried melatonin to help with circadian disturbances during medical school I slept beautifully, but with horrendous nightmares (e.g. I couldn’t save my drowning parrot and, another time, dreamed I was walking across the Golden Gate Bridge on a windy day and the side rails had been removed. A lesser nightmare was a visit from an angry Pope John Paul asserting that I was making crank calls to the Vatican.I felt guilty even though I didn’t do it…and I’m Jewish).

Zolpidem (e.g. Ambien) and other sedative-hypnotic agents like lorazepam, temazepam and alprazolam (e.g. Ativan, Restoril and Xanax, respectively): Disruption of sleep is a major factor in the unpleasantness and general morbidity associated with jet lag. A lot attention has been given to the use of sedative-hypnotics for the induction and maintenance of sleep. Each of the medications listed above has a different half-life and utility depending on the types of disordered sleep encountered by different people. Briefly, zolpidem has a short half-life, but works quickly (~30 minutes) and it often used to help initiate sleep. If getting to sleep is harder than maintaining it, a medication such as zolpidem or alprazolam might be most effective in ameliorating symptoms of sleep disruption. A longer acting medication such as temazepam should be considered for those with more difficulty maintaining sleep.

Adverse Effects:
As with all medications the intended, salutary, effects need to be balanced with the risks. For example, alprazolam interacts with a lot of other medications, such as warfarin. In addition, ALL benzodiazepines (generally your drugs with the suffixes, “-pam” and “lam”, but including Librium) are verboten in pregnancy, “Class D” (Dangerous). Women of child-bearing age who have any chance of being pregnant should not take these drugs. Benzodiazepines act on the same basic receptors as alcohol and cause the same general types of birth defects as seen with fetal alcohol syndrome (FAS).Nevertheless, if an isolated dose or doses are taken prior to the discovery of pregnancy, it is not cause for panic. Like alcohol, the dose and chronicity make the poison—just stop and talk to your physician about any further evaluation or testing that might be warranted.As with pregnancy, all benzodiazepines are considered Dangerous in lactation. Nursing mothers should not take these medications. Adverse effects from benzodiazepines include those described during pregnancy and also include amnesia, grogginess, interactions with other medications and severe withdrawal syndromes and addiction, such that people occasionally die from withdrawal seizures. The potential for abuse of these medications is fairly high. If you have had problems with substance abuse/addiction, including with alcohol, these medications should probably be studiously avoided for elective use.That being said, the short-term benefits of having a good night of sleep cannot be underestimated—in the absence of addiction issues and the use of medications with adverse interactions with these drugs.

Zolpidem (Ambien) is considered to be fairly safe in pregnancy (“Class B”…presumed safe based on animal studies) and is generally accepted to be safe during lactation for the children of nursing mothers. I generally favor this specific medication for lactating or pregnant/potentially pregnant women.Relatively common side effects include amnesia (e.g. not remembering any of the words played in last night’s unfinished Scrabble game), confusion, nausea and erratic behavior. If you made out with the passenger next to you and don’t remember it having happened when he/she asked for your number (erratic + amnesia)…this is not the medication for you. The former happened to me and the latter to a friend. That is the absolute truth.

Pharmacological interventions you can expect to see approved by the FDA in the near future: Modafinil (e.g. Provigil). This is an interesting drug approved for use in narcolepsy and in shift-work sleep disorder. It is generally taken 1 hour prior to starting a shift. Jet lag and shift-work sleep disorders have a lot in common with respect to disrupted sleep and overall circadian disturbance.Most recently, Phase III clinical trials have been completed and published with seemingly good results. Interestingly, sildenafil citrate (aka “Viagra”) has been shown to enhance adaptation to changing light schedules…in hamsters.In this study, out of Argentina, a dose of 3.5 mg/kg (or about 245 mg for a 70 kg male) was injected into the hamsters to achieve this effect.  I didn’t read the study all that carefully but didn’t see any comments other than those about circadian re-entrainment and I was left to ponder, “Were they breeding like rabbits?” Viagra for humans with erectile dysfunction is generally given in increments of 25, 50 and 100mg and I imagine that at hamster doses it would cause significant nasal congestion and a blistering headache. I think this one is a long way away from approval for use in jet lag.

Admonitions:
Don’t get prescriptions that are likely to last any longer than you actually need (a five or six day supply) Don’t drive when tired or having taken any of these medications in the past 6 hours Don’t mix with alcohol. Don’t accept medications from friends…we recently saw the case of a patient who was given doses of his friend’s “sleeping pills,” that turned out to be methadone and a fatal overdose, at that. Plan ahead and get a proper prescription. If you are taking medications for which blood levels are measured (e.g. warfarin, lithium, carbamezapine, digoxin) then there is a good chance they interact with alprazolam and other medications or foods in an unsafe way.Others that commonly interact with food or drugs include anti-cholesterol drugs in the –statin class (grapefruit juice inhibits the enzyme that breaks down the drug with potentially fatal consequences) and MAOI and mixed-MAOI inhibitors. Avoiding caffeine and alcohol: Generally not recommended, yet no systematic study of these “self-medications” has ever been undertaken. I don’t recommend them, but more than that would be confusing fact with opinion. This is so far from a complete list of admonitions that you really need to talk to your doctor.

Be Positive!
1. You will not be more tired than usual for the rest of your life. 2. Thoughtful planning of sleep and wake times during travel can shorten the duration of symptoms from jet lag. 3. Being happy to be home and seeing your family, friends and colleagues is probably the best remedy. I won’t remember having written this, tomorrow, but feel free to correspond. I welcome any comments, suggestions and useful criticisms. I will do my best to respond promptly. SAFE TRAVELS!